Welsh Gavin I, Coward Richard J M
Academic and Children's Renal Unit, Bristol University, Southmead Hospital, Bristol, UK.
Curr Opin Nephrol Hypertens. 2010 Jul;19(4):379-84. doi: 10.1097/MNH.0b013e32833ad5e4.
In the last decade the importance of the podocyte in maintaining the integrity of the glomerular filtration barrier and prevention of albuminuria has become obvious. The leading cause of renal failure in the developed world is diabetic nephropathy. This has a defined natural history of progressive albuminuria. The two fundamental cellular changes that occur in diabetes mellitus are a failure of insulin to signal to cells and an environment of hyperglycaemia. The emerging role of these factors on the biological function of the podocyte will be reviewed.
Hyperglycaemia causes both deleterious and protective cellular pathways to be initiated in the podocyte, which communicate with other cell types in the glomerulus. Furthermore, the podocyte is an insulin-sensitive cell which can be directly modulated by factors that increase and decrease its sensitivity to insulin.
Our understanding of the cellular processes that affect the podocyte in diabetes and insulin resistance has progressed greatly in recent years and hopefully will result in new treatment strategies against the leading cause of renal failure in the developed world.
在过去十年中,足细胞在维持肾小球滤过屏障完整性及预防蛋白尿方面的重要性已变得十分明显。在发达国家,肾衰竭的主要原因是糖尿病肾病。其具有明确的进行性蛋白尿自然病程。糖尿病发生的两个基本细胞变化是胰岛素向细胞传递信号失败以及高血糖环境。本文将综述这些因素对足细胞生物学功能的新作用。
高血糖在足细胞中引发有害和保护性细胞途径,这些途径与肾小球中的其他细胞类型相互作用。此外,足细胞是一种胰岛素敏感细胞,可被增加或降低其对胰岛素敏感性的因素直接调节。
近年来,我们对糖尿病和胰岛素抵抗中影响足细胞的细胞过程的理解有了很大进展,有望由此产生针对发达国家肾衰竭主要原因的新治疗策略。